Intensity dependent estimation of noise in microarrays improves detection of differentially expressed genes

Background  

In many microarray experiments, analysis is severely hindered by a major difficulty: the small number of samples for which expression data has been measured. When one searches for differentially expressed genes, the small number of samples gives rise to an inaccurate estimation of the experimental noise. This, in turn, leads to loss of statistical power.     

Regulated oligomerisation and molecular interactions of the early gametocyte protein Pfg27 in Plasmodium falciparum sexual differentiation

Gametocytes of the protozoan Plasmodium falciparum ensure malaria parasite transmission from humans to the insect vectors. In their development, they produce the abundant specific protein Pfg27, the function and in vivo molecular interactions of which are unknown. Here we reveal a previously unreported localisation of Pfg27 in the gametocyte nucleus by immunoelectron microscopy and studies with HaloTag and Green Fluorescent Protein fusions, and identify a network of interactions established by the protein during gametocyte development. We report the ability of endogenous Pfg27 to form oligomeric complexes that are affected by phosphorylation of the protein, possibly through the identified phosphorylation sites, Ser32 and Thr208. We show that Pfg27 binds RNA molecules through specific residues and that the protein interacts with parasite RNA-binding proteins such as EF1α and PfH45. We propose a structural model for Pfg27 oligomerisation, based on the sequence and structural conservation here recognised between Pfg27 and sterile alpha motif. This study provides a molecular basis for Pfg27 to establish an interaction network with RNA and RNA-binding proteins and to govern its dynamic oligomerisation in developing gametocytes.     

Threshold policies control for predator-prey systems using a control Liapunov function approach

The stability of predator-prey models, in the context of exploitation of renewable resources, subject to threshold policies (TP) is studied in this paper using the idea of backstepping and control Liapunov functions (CLF) well known in control theory, as well as the concept of virtual equilibria. TPs are defined and analysed for different types of one and two species predator-prey models. The models studied are the single species Noy-Meir herbivore-vegetation model, in a grazing management context, as well as the Rosenzweig-MacArthur two species predator-prey model, in a fishery management context. TPs are shown to be versatile and useful in managing renewable resources, being simple to design and implement, and also yielding advantages in situations of overexploitation.     

Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis

Although recent animal studies have fuelled growing interest in Ab-independent functions of B cells, relatively little is known about how human B cells and their subsets may contribute to the regulation of immune responses in either health or disease. In this study, we first confirm that effector cytokine production by normal human B cells is context dependent and demonstrate that this involves the reciprocal regulation of proinflammatory and anti-inflammatory cytokines. We further report that this cytokine network is dysregulated in patients with the autoimmune disease multiple sclerosis, whose B cells exhibit a decreased average production of the down-regulatory cytokine IL-10. Treatment with the approved chemotherapeutic agent mitoxantrone reciprocally modulated B cell proinflammatory and anti-inflammatory cytokines, establishing that the B cell cytokine network can be targeted in vivo. Prospective studies of human B cells reconstituting following in vivo depletion suggested that different B cell subsets produced distinct effector cytokines. We confirmed in normal human B cell subsets that IL-10 is produced almost exclusively by naive B cells while the proinflammatory cytokines lymphotoxin and TNF-alpha are largely produced by memory B cells. These results point to an in vivo switch in the cytokine "program" of human B cells transitioning from the naive pool to the memory pool. We propose a model that ascribes distinct and proactive roles to memory and naive human B cell subsets in the regulation of memory immune responses and in autoimmunity. Our findings are of particular relevance at a time when B cell directed therapies are being applied to clinical trials of several autoimmune diseases.     

Mechanism for Amyloid Precursor-like Protein 2 Enhancement of Major Histocompatibility Complex Class I Molecule Degradation

Earlier studies have demonstrated interaction of the murine major histocompatibility complex (MHC) class I molecule K^d with amyloid precursor-like protein 2 (APLP2), a ubiquitously expressed member of the amyloid precursor protein family. Our current findings indicate that APLP2 is internalized in a clathrin-dependent manner, as shown by utilization of inhibitors of the clathrin pathway. Furthermore, we demonstrated that APLP2 and K^d bind at the cell surface and are internalized together. The APLP2 cytoplasmic tail contains two overlapping consensus motifs for binding to the adaptor protein-2 complex, and mutation of a tyrosine shared by both motifs severely impaired APLP2 internalization and ability to promote K^d endocytosis. Upon increased expression of wild type APLP2, K^d molecules were predominantly directed to the lysosomes rather than recycled to the plasma membrane. These findings suggest a model in which APLP2 binds K^d at the plasma membrane, facilitates uptake of K^d in a clathrin-dependent manner, and routes the endocytosed K^d to the lysosomal degradation pathway. Thus, APLP2 has a multistep trafficking function that influences the expression of major histocompatibility complex class I molecules at the plasma membrane.     

Antioxidant response in sesame plants grown on industrially contaminated soil: effect on oil yield and tolerance to lipid peroxidation

The plants of sesame white (Sesamum indicum L. var. T55) grown on tannery sludge (TS) contaminated soil have shown that Cr level in the seeds was found below detection limits in 10% and 25% TS, however, the levels of Ni, Pb and Cd were found above the recommended limits. In roots, the level of antioxidants increased in the plants grown upto 35% TS at 30d over their respective controls. Total chlorophyll content increased significantly (p<0.5) in the plants (leaves) grown on lower sludge amendments (upto 35% TS at 30d and 25% TS at 60d) over their respective controls. In addition, the oil content increased (35% increase over control) in the plants grown on 35% TS. No significant change was observed in thiobarbituric acid reactive substances (TBARS), a lipid peroxidation index, in the plants (upto 50% TS). The number of trichomes in the leaves of treated plants was found more than control. In lower and upper leaves surfaces, the anterior end of the trichomes was found acute tipped and bent downwards, whereas, the trichome tip was straight and blunt in control. The stomata on upper and lower surfaces of the leaves were found partially or totally closed in the plants grown on 100% TS as compared to control. The toxicity was observed at higher amendments which are evident from the observed morphological changes and decrease in chlorophyll content. This study concludes that it is not advisable to grow the plants on contaminated area, besides its healthy growth.     

Beyond pollinator attraction: extra-floral displays deter herbivores in a Mediterranean annual plant

The evolution of several floral traits is thought to be driven by multiple selective agents, including pollinators and herbivores. Similar combinations of selection pressures may have shaped extra-floral traits. The conspicuous purple tufts of leaves (“flags”), which often terminate vertical inflorescences in the Mediterranean annual Salvia viridis, were shown to attract insect pollinators to the flowering patch. Here we test whether they also function as anti-herbivore signals. We determined the aposematic potential of S. viridis flags on three levels: concentrations of anthocyanins, suggested to function as aposematic visual signals, in leaves and flags; spectrometry to estimate whether the color-vision system of two common Mediterranean generalist herbivores (locusts and goats) can discriminate flags from leaves; and choice experiments to determine food preferences of the same herbivores. Anthocyanin concentrations in flags were >10-fold higher than in leaves. Flags exhibited peak reflectance at 450 and 700 nm wavelengths, while leaves reflected maximally at 550 nm. According to the Vorobyev-Osorio color vision model, these differences in color reflection are likely to allow visual discrimination by herbivores. Goats preferred feeding on clipped inflorescences over control inflorescences. Locusts preferred leaves over flags. To test whether this was due to deterrence from the flags’ coloration, we also offered them choice between leaves and a rare, white morph, of the flags. The locusts chose both equally immediately after presentation, but leaves attracted more individuals after 5 min of feeding. The locusts also preferred green cabbage over anthocyanin-rich red cabbage. These results support the function of colorful extra-floral displays as warning signals.     

Light and temperature regulated terpene biosynthesis: hepatoprotective monoterpene picroside accumulation in Picrorhiza kurrooa

Picrorhiza (Picrorhiza kurrooa) is an endangered medicinal plant with well-known hepatoprotective activity attributed to monoterpenoid picrosides. The present article details on regulatory genes of terpenoid metabolism, 3-hydroxy-3-methylglutaryl coenzyme A reductase (pkhmgr) and 1-deoxy-D-xylulose-5-phosphate synthase (pkdxs) from picrorhiza. Since no molecular information was available, these genes were cloned to full-length by degenerate primers and rapid amplification of cDNA ends, followed by cloning of the upstream sequences that showed the presence of core sequences for light and temperature responsiveness. Electrophoretic mobility shift assay confirmed binding of protein to these motifs. Expression of pkhmgr and pkdxs was up-regulated at 15°C as compared to at 25°C as well as under light as compared to dark conditions. Picrosides content exhibited the trend similar to gene expression. To rule out the possible limitation of carbon pool under dark condition, plantlets of picrorhiza were raised in vitro in Murashige and Skoog medium supplemented with 3% sucrose. Results showed similar up-regulation of both the genes and the higher picrosides content in in vitro raised plantlets in the presence of light. Data suggested the important roles played by light and temperature in regulating pkhmgr and pkdxs, and the picrosides level in picrorhiza.